The Programmed Death-1 (PD-1) protein, also known as CD279, is an inhibitory receptor that belongs to the CD28 family of receptors. PD-1 is expressed on activated T cells, B cells, and myeloid cells and contains a membrane proximal immune-receptor tyrosine inhibitory motif (ITIM) and a membrane distal tyrosine-based switch motif (ITSM). PD-1 has been reported as an immune checkpoint, and to serve an important role in down-regulating the immune system by preventing the activation of T cells. Ligation of PD-1 by its ligands has been found to generate an inhibitory signal that results in reduced cytokine production, and reduced T cell survival. Two ligands for PD-1 have previously been identified, which have been referred to, in the prior art, as programmed death-ligand 1 (PD-L1) (B7-H1) and programmed death-ligand 2 (PD-L2) (B7-DC), and have been shown to down-regulate T cell activation upon binding to PD-1. Moreover, the interaction between PD-1 and PD-L1 has also been found to result in a decrease in tumor infiltrating lymphocytes, a decrease in T-cell receptor mediated proliferation, and immune evasion by the cancerous cells.
In view of the foregoing, it would be desirable to identify and develop one or more peptides that are effective to compete with PD-L1 and/or PD-L2 for binding to PD-1, which may thereby inhibit PD-1/PD-L1 and/or PD-1/PD-L2 interactions. Such inhibitory effects will preferably be useful in preventing, treating, and/or ameliorating the effects of various types of cancers. As the following will demonstrate, the present invention provides such peptides, methods for using such peptides, and other advantages described herein.